The development of molecularly imprinted polymer nanoparticles for cancer theranostics

该项目的目标是开发能够靶向癌症生物标志物的分子印迹聚合物（MIPs），用于递送成像和治疗剂。这包括使用新开发的基于MIP的技术进行细胞和蛋白质的表位作图，以鉴定临床相关的生物标志物。该项目的主要目标是表皮生长因子受体（EGFR），一种由多种癌细胞过度表达的跨膜蛋白。选择几种细胞系（包括乳腺和头颈部），因为它们具有高表达水平的EGFR，并进行基于MIP的表位作图。分析了使用该技术鉴定的肽的源蛋白和细胞位置（细胞内、跨膜或细胞外）。分离EGFR肽，并基于特定细胞类型或细胞内位置的丰度选择几个序列用于进一步研究。这些肽从商业供应商订购，用作生成MIP纳米颗粒的模板分子。这些纳米颗粒将用荧光或PET活性剂标记，用于标记细胞内的EGFR。这将对进行表位作图的每种细胞类型进行，以验证基于MIP的表位作图作为鉴定生物标志物和表位的定量技术。该项目的最后一个方面将是通过掺入含硼单体来提供治疗剂，包括用于硼中子捕获治疗（BNCT）的硼。

The goal of this project is the development of molecularly imprinted polymers (MIPs) capable of targeting cancer biomarkers for the delivery of imaging and therapeutic agents. This includes the use of a newly-developed MIP-based technique for epitope mapping of cells and proteins, in order to identify clinically-relevant biomarkers. The primary target of this project is epidermal growth factor receptor (EGFR), a transmembrane protein over-expressed by a variety of cancer cells. Several cell lines (including breast and head and neck) were selected for their high expression levels of EGFR and MIP-based epitope mapping was performed. The peptides identified using this technique were analysed both with regards to source protein and cellular location (intracellular, transmembrane or extracellular). The EGFR peptides were isolated and several sequences selected for further study based on abundance on specific cell types or location within the cell. These peptides were ordered from a commercial provider for use as template molecules for the generation of MIP nanoparticles. These nanoparticles are to be tagged with fluorescent or PET-active agents for use in labelling EGFR within cells. This will be undertaken with each cell type for which epitope mapping was performed in order to validate MIP-based epitope mapping as a quantitative technique for the identification of biomarkers and epitopes. The final aspect of the project will be the delivery of therapeutic agents including boron for boron neutron capture therapy (BNCT) via incorporation of a boron-containing monomer.